Hypoxia Promotes Glycogen Accumulation through Hypoxia Inducible Factor (HIF)-Mediated Induction of Glycogen Synthase 1
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{"title"=>"Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1", "type"=>"journal", "authors"=>[{"first_name"=>"Nuria", "last_name"=>"Pescador", "scopus_author_id"=>"8706717500"}, {"first_name"=>"Diego", "last_name"=>"Villar", "scopus_author_id"=>"8706717200"}, {"first_name"=>"Daniel", "last_name"=>"Cifuentes", "scopus_author_id"=>"8623178600"}, {"first_name"=>"Mar", "last_name"=>"Garcia-Rocha", "scopus_author_id"=>"6603753936"}, {"first_name"=>"Amaya", "last_name"=>"Ortiz-Barahona", "scopus_author_id"=>"35867558200"}, {"first_name"=>"Silvia", "last_name"=>"Vazquez", "scopus_author_id"=>"57196996645"}, {"first_name"=>"Angel", "last_name"=>"Ordoñez", "scopus_author_id"=>"7007153220"}, {"first_name"=>"Yolanda", "last_name"=>"Cuevas", "scopus_author_id"=>"6507959965"}, {"first_name"=>"David", "last_name"=>"Saez-Morales", "scopus_author_id"=>"35785186400"}, {"first_name"=>"Maria Laura", "last_name"=>"Garcia-Bermejo", "scopus_author_id"=>"34770993200"}, {"first_name"=>"Manuel O.", "last_name"=>"Landazuri", "scopus_author_id"=>"6602990148"}, {"first_name"=>"Joan", "last_name"=>"Guinovart", "scopus_author_id"=>"7005429593"}, {"first_name"=>"Luis", "last_name"=>"Del Peso", "scopus_author_id"=>"6701726130"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"77950523330", "doi"=>"10.1371/journal.pone.0009644", "pui"=>"358582244", "pmid"=>"20300197", "scopus"=>"2-s2.0-77950523330", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"19e355ef-300f-3066-99a5-bcecf0ea6caa", "abstract"=>"When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1alpha or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-alpha glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia.", "link"=>"http://www.mendeley.com/research/hypoxia-promotes-glycogen-accumulation-through-hypoxia-inducible-factor-hifmediated-induction-glycog", "reader_count"=>106, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>6, "Researcher"=>23, "Student > Doctoral Student"=>11, "Student > Ph. D. Student"=>38, "Student > Postgraduate"=>3, "Student > Master"=>9, "Other"=>3, "Student > Bachelor"=>8, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>6, "Researcher"=>23, "Student > Doctoral Student"=>11, "Student > Ph. D. Student"=>38, "Student > Postgraduate"=>3, "Student > Master"=>9, "Other"=>3, "Student > Bachelor"=>8, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>25, "Agricultural and Biological Sciences"=>50, "Medicine and Dentistry"=>13, "Neuroscience"=>2, "Sports and Recreations"=>2, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1, "Chemistry"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>4}, "Sports and Recreations"=>{"Sports and Recreations"=>2}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>50}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>25}, "Unspecified"=>{"Unspecified"=>7}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>3, "Ireland"=>2, "Brazil"=>1, "United Kingdom"=>3, "France"=>3, "Portugal"=>1, "Spain"=>1}, "group_count"=>1}

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  • {"files"=>["https://ndownloader.figshare.com/files/859155"], "description"=>"<p>(A) Schematic representation of human GYS1 genomic region from -429 to +298 showing evolutionarily conserved regions. Adapted from the UCSC Genome Browser (<a href=\"http://genome.ucsc.edu/\" target=\"_blank\">http://genome.ucsc.edu/</a>). The lines above the graph show the genomic regions cloned in the indicated reporter constructs (see text). The inset under the figure represents the sequence alignment of the HRE element from the indicated species. (B) c2c12 cells exposed to 21% (Nx) or 1% (Hx) oxygen for 12 hours and then fixed and processed for chromatin immunoprecipitation with anti-HIF1α (HIF1α) antibodies or control IgG (IgG). (Input) lanes correspond to total sonicated genomic DNA. After immunoprecipitation, chromatin was amplified with primers specific for the HRE-containing genomic regions from GYS1. The HIF binding region within the Procollagen 4-hydroxylase α (P4Hα) was included as a positive control <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009644#pone.0009644-Pescador1\" target=\"_blank\">[25]</a>. (C, D) HeLa cells transfected with a reporter plasmid containing GYS1 genomic region (-210 to -419) upstream of a minimal promoter (C) or a plasmid containing the whole GYS promoter region (+128 to -419) driving the expression of a luciferase reporter gene (D). Where indicated (mutHRE) the consensus HRE sequence (ACGT) was mutated to TAGC. The graphs represent the corrected luciferase activity values of each construct over the luciferase activity obtained in normoxic cells transfected with empty plasmids (control). Data shown are the results of four independent experiments and their mean (bar and numbers on the right).</p>", "links"=>[], "tags"=>["hre", "gys1", "genomic"], "article_id"=>529601, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_a_functional_HRE_in_GYS1_genomic_region_/529601", "title"=>"Identification of a functional HRE in GYS1 genomic region.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:40:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/859319"], "description"=>"<p>c2c12 myoblasts were incubated at 21% (Nx) or 1% oxygen (Hx) for the indicated periods of time and processed to determine GYS1/pGYS1(phospho-Ser 641) levels (A) and glycogen synthase activity in the absence (B) or presence of 6.6 mM of the allosteric modulator glucose-6-phospate (C). Graphs represent the mean of duplicated measures and error bars the range. (D) The graph represents the ratio of glycogen synthase activity in the absence (I) and presence (T) of glucose-6-phosphate. The experiment was repeated twice with similar results.</p>", "links"=>[], "tags"=>["increases", "glycogen", "synthase"], "article_id"=>529764, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hypoxia_increases_glycogen_synthase_activity_/529764", "title"=>"Hypoxia increases glycogen synthase activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:42:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/859000"], "description"=>"<p>c2c12 myoblasts were transfected with siRNA against mouse HIF1α (HIF1α), an siRNA containing an irrelevant sequence (Scramble) or left untreated (none). 24 hours after transfection cells were cultured for 12 hours at 21% (Nx) or 1% oxygen (Hx) and then processed to determine mRNA (A,C), or protein (B) levels. Graphs represent normalized mRNA levels in each condition relative to the untreated normoxic cells. Data shown are the results of three independent experiments and their mean. **, p<0.01 as compared to samples transfected with irrelevant siRNA (Control) and exposed to the same oxygen tension. Numbers represent average values. (D) HIF-competent (HIFβ wt), Hepa C1, and HIF-deficient (HIFβ def), Hepa C4, cells were exposed to normoxia (Nx) or 1% oxygen (Hx) for 12 hours and processed to determine GYS1 mRNA level. The graph represents the normalized GYS1 mRNA levels in each condition relative to the normoxic Hepa C1 cells (horizontal line) from three independent experiments. **, p<0.01 as compared to HIF-competent cells exposed to the same oxygen tension.</p>", "links"=>[], "tags"=>["mediates", "gys1", "induction"], "article_id"=>529448, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g002", "stats"=>{"downloads"=>3, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIF_mediates_GYS1_induction_by_hypoxia_/529448", "title"=>"HIF mediates GYS1 induction by hypoxia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:37:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/859774"], "description"=>"<p>(A) c2c12 myoblast and primary mouse hepatocytes were exposed to normoxia or hypoxia for 12 hours and the level of UGP2 and GBE1 mRNA was determined by quantitative PCR. The amount of each mRNA in samples was normalized to the content of β-actin mRNA in the same sample. Data shown represent the fold values of hypoxic over normoxic mRNA levels normalized to the value of 1 (horizontal line) in three independent experiments. (B) c2c12 myoblasts were exposed to normoxia (Nx) or hypoxia (Hx) for 24 hours and the activity of glycogen phosphorylase was assayed in untreated cell lysates, or in the presence of cAMP or caffeine. The results from five independent experiments and their mean are shown. (C) c2c12 myoblasts and primary mouse hepatocytes (Hepato) were exposed to normoxia or hypoxia for 12 hours and the level of PYGM, PYGB and PYGL mRNA was determined by quantitative PCR. The amount of each mRNA in samples was normalized to the content of β-actin mRNA in the same sample. Data shown represent the fold values of hypoxic over normoxic mRNA levels normalized to the value of 1 (horizontal line) in three independent experiments.</p>", "links"=>[], "tags"=>["affects", "glycogen", "metabolism"], "article_id"=>530218, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g008", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hypoxia_affects_glycogen_metabolism_at_multiple_levels_/530218", "title"=>"Hypoxia affects glycogen metabolism at multiple levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 00:03:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/858908"], "description"=>"<p>c2c12 myotubes (A) or primary mouse hepatocytes (B) were exposed to normoxia or hypoxia for 12 hours and the level of GYS1 and GYS2 mRNA was determined by quantitative PCR. The amount of each mRNA in samples was normalized to the content of β-actin mRNA in the same sample. The graph represents the fold values of hypoxic over normoxic mRNA levels normalized to the value of 1 (horizontal line). Data shown are the results of three independent experiments and their mean. (C) c2c12 cells were treated with 1 µg/ml actinomycin D (Act.D) or vehicle (control) for 30 minutes and then exposed to normoxia or 1% oxygen (Hypoxia) for 12 hours. The graph represents GYS1 mRNA levels in each condition relative to the untreated (control) normoxic cells. The experiment was repeated twice with identical results.</p>", "links"=>[], "tags"=>["hypoxia-regulated", "hif"], "article_id"=>529359, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g001", "stats"=>{"downloads"=>5, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GYS1_but_not_GYS2_is_a_hypoxia_regulated_HIF_target_gene_/529359", "title"=>"GYS1, but not GYS2, is a hypoxia-regulated HIF target gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:35:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/859911"], "description"=>"<p>Hepa C1 and Hepa C4 cells (A) or Hepa C1 cells stably expressing a shRNA directed to GYS1 or a control shRNA (B) were exposed to 21% (Nx->Ax) or 1% (Hx->Ax) for 24 hours in complete media and then cultured in a glucose-free serum-free media and anoxia for 12 additional hours. Cell viability was determined as indicated in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009644#s4\" target=\"_blank\">Materials and Methods</a>. The results from four independent experiments and their mean are shown.</p>", "links"=>[], "tags"=>["contributes", "hypoxic"], "article_id"=>530356, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g009", "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GYS1_contributes_to_hypoxic_preconditioning_/530356", "title"=>"GYS1 contributes to hypoxic preconditioning.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 00:05:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/859431"], "description"=>"<p>C2c12 myotubes (A), inmortalized mouse hepatocytes (B) and mouse hepatoma Hepa C1 cells (B), were exposed to normoxia or hypoxia (1% Oxygen) for the indicated periods of time and glycogen content was determined. Graphs represent average measures of glycogen content in two independent samples and error bars the range. Data shown are representative of at least five (A) or two (B) independent experiments.</p>", "links"=>[], "tags"=>["induces", "glycogen"], "article_id"=>529877, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g005", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hypoxia_induces_glycogen_accumulation_/529877", "title"=>"Hypoxia induces glycogen accumulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:44:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/859532"], "description"=>"<p>(A) c2c12 myoblasts were transfected with siRNA against mouse HIF1α (HIF1α), siRNA containing an irrelevant sequence (Control) or left untreated (none). After transfection cells were cultured for 12 hours under normoxia or 1% oxygen (Hypoxia) and processed to determine glycogen content. Graphs represent the average of two independent determinations and their range. Data shown are representative of three independent experiments. (B) Hepa C1 and Hepa C4 cells were exposed to 21% (Normoxia) or 1% oxygen (Hypoxia) for 12 hours and processed to determine their glycogen content. Graphs represent the mean of duplicated measures and error bars the range, results shown are representative of three independent experiments.</p>", "links"=>[], "tags"=>["glycogen", "accumulation"], "article_id"=>529974, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hypoxia_driven_glycogen_accumulation_is_HIF_dependent_/529974", "title"=>"Hypoxia-driven glycogen accumulation is HIF-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 02:46:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/859630"], "description"=>"<p>c2c12 myoblasts were transfected with siRNA against mouse GYS1 (GYS1), siRNA containing an irrelevant sequence (Control). 24 hours after transfections cells were cultured for 12 hours under 21% (Nx) or 1% oxygen (Hx), then each sample was split and processed to determine GYS1 mRNA (A), protein levels (B) or glycogen content (C). The experiment was repeated twice with similar results. GYS1 mRNA levels (D) and glycogen content (E) were determined in Hepa C1 cells stably expressing a shRNA directed to GYS1 or a control shRNA. Results from four independent experiments are represented. *, p<0.05; **, p<0.01; as compared to samples expressing control shRNA and exposed to normoxia. (F) c2c12 myotubes were infected with AdGYS1 or Adβ-Gal. 24 hours after infection cells were processed for glycogen content determination. Parallel cultures were exposed to normoxia or hypoxia for 12 hours and processed for glycogen determination. Graphs represent the mean of duplicated measures and error bars the range, the experiment was repeated twice with similar results.</p>", "links"=>[], "tags"=>["mediates", "glycogen", "accumulation"], "article_id"=>530071, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0009644.g007", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GYS1_mediates_glycogen_accumulation_during_hypoxia_/530071", "title"=>"GYS1 mediates glycogen accumulation during hypoxia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-03-12 00:01:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/426863", "https://ndownloader.figshare.com/files/426878"], "description"=>"<div><p>When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1α or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-α glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia.</p></div>", "links"=>[], "tags"=>["hypoxia", "promotes", "glycogen", "accumulation", "inducible", "induction", "synthase"], "article_id"=>144260, "categories"=>["Cell Biology", "Biochemistry"], "users"=>["Nuria Pescador", "Diego Villar", "Daniel Cifuentes", "Mar Garcia-Rocha", "Amaya Ortiz-Barahona", "Silvia Vazquez", "Angel Ordoñez", "Yolanda Cuevas", "David Saez-Morales", "Maria Laura Garcia-Bermejo", "Manuel O. Landazuri", "Joan Guinovart", "Luis del Peso"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0009644.s001", "https://dx.doi.org/10.1371/journal.pone.0009644.s002"], "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Hypoxia_Promotes_Glycogen_Accumulation_through_Hypoxia_Inducible_Factor_HIF_Mediated_Induction_of_Glycogen_Synthase_1/144260", "title"=>"Hypoxia Promotes Glycogen Accumulation through Hypoxia Inducible Factor (HIF)-Mediated Induction of Glycogen Synthase 1", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-03-12 01:11:00"}

PMC Usage Stats | Further Information

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Relative Metric

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